The biological relevance of FHL2 in tumour cells and its role as a putative cancer target.

The LIM-only protein FHL2 (four-and-a-half LIM-domain protein 2) belongs to the FHL protein family of transcriptional cofactors present in various cell lines. FHL2 interacts with a variety of transcription factors known to be involved in tumour development. Furthermore, FHL2 expression is often deregulated in cancer including overexpression and down-regulation in various types of tumours. The function of FHL2 in cancer is particularly intriguing, since it may act as an oncoprotein or as a tumour suppressor in a tissue-dependent fashion. This dual nature of FHL2 is also reflected by the finding that it can function as repressor or activator of transcriptional activity depending on the cell-type. The ability of FHL2 to exert functional diversity lies within its structural composition as a LIM-only protein. LIM-domains are enzymatically inactive protein-to-protein interaction domains, which determine the function of LIM-only proteins as adaptor molecules or scaffolding proteins. By selectively using different LIM-domains for protein-to-protein interactions, FHL2 is capable to interact with a broad spectrum of functionally unrelated proteins, thereby triggering different signalling pathways. In this review, the current knowledge of FHL2 expression in different cancers was summarized and the interaction of FHL2 with transcription factors and other proteins involved in cancer development was examined. Since transcription factors control all fundamental developmental and homeostatic processes, transcriptional cofactors like FHL2 are likely to contribute to human carcinogenesis and are of clinical importance in various forms of cancer.